Multinuclear Fourier-transform nuclear magnetic resonance spectroscopy will be used in conjunction with a perfusable gel matrix to study the intracellular chemistry of the cytoxan metabolites 4-hydroxy-cytoxan (4-hydroxycyclophosphamide) aldophosphamide, and phosphoramide mustard. The influence of metabolite structure and stereochemistry on the kinetics of cellular uptake, intracellular detoxification, and intracellular toxicogenation in normal versus neoplastic cells will be investigated using metabolite-analogs. These studies will probe those factors of cytoxan metabolism which are pertinent to its oncostatic selectivity. A series of novel lipophilic analogs of aldophosphamide will be synthesized and tested for their anticancer activity against brain tumors.